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Un colectivo de factores de transcripción define el destino de las células cardíacas y refleja la historia del linaje
Guillaume Junion1, Mikhail Spivakov, Charles Girardot
1Genome Biology Unit, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.
Cell
|February 7, 2012
Resumen
La especificación cardíaca en Drosophila involucra factores de transcripción (TF) y vías de señalización. Estos TFs regulan cooperativamente la actividad del potenciador cardíaco, mostrando la flexibilidad del motivo y una huella molecular potencial para el linaje de desarrollo.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- Genética La genética.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Las decisiones sobre el destino celular integran señales inductivas y factores de transcripción (TF).
- Los mecanismos de convergencia de TF en elementos cis-reguladores para la expresión génica específica de la célula no se comprenden completamente.
- Comprender la especificación cardíaca requiere aclarar cómo los componentes genéticos coordinan la actividad del potenciador.
Objetivo del estudio:
- Investigar cómo los componentes genéticos esenciales para la especificación cardíaca en Drosophila cooperan para regular la actividad del potenciador cardíaco.
- Explorar la flexibilidad vinculante y las implicaciones funcionales de la vinculación combinatoria de TF.
- Identificar las firmas moleculares potenciales del linaje del desarrollo en elementos cis-reguladores.
Principales métodos:
- Ensayos in vivo e in vitro para evaluar la actividad del potenciador cardíaco.
- Análisis de la unión combinatoria de cinco componentes genéticos clave para la especificación cardíaca.
- Mutagénesis dirigida al sitio para investigar el papel de sitios específicos de unión de TF.
Principales resultados:
- Los cinco componentes genéticos para la especificación cardíaca actúan como una unidad cooperativa para regular la actividad del potenciador cardíaco.
- La unión combinatoria TF demuestra una amplia flexibilidad de motivos, independientemente de la orientación o el espaciado.
- Un subconjunto de potenciadores mostró actividad en el mesodermo visceral, que podría ser redirigido al corazón a través de mutaciones de un solo sitio.
Conclusiones:
- La unión TF cooperativa con la flexibilidad del motivo es un mecanismo clave en la regulación de la actividad del potenciador cardíaco.
- Las firmas de enlace TF "dormidas" en tejidos relacionados pueden reflejar orígenes de desarrollo compartidos.
- Este estudio proporciona información sobre la lógica reguladora de las decisiones del destino celular y el linaje del desarrollo.
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